Anti-cancer activity of anti-GLUT1 antibody-targeted polymeric micelles co-loaded with curcumin and doxorubicin

J Drug Target. 2013 Dec;21(10):994-1000. doi: 10.3109/1061186X.2013.840639. Epub 2013 Oct 7.

Abstract

Background: Treatment of late stage cancers has proven to be a very difficult task. Targeted therapy and combinatory drug administration may be the solution.

Purpose: The study was performed to evaluate the therapeutic efficacy of PEG-PE micelles, co-loaded with curcumin (CUR) and doxorubicin (DOX), and targeted with anti-GLUT1 antibody (GLUT1) against HCT-116 human colorectal adenocarcinoma cells both in vitro and in vivo.

Methods: HCT-116 cells were treated with non-targeted and GLUT1-targeted CUR and DOX micelles as a single agent or in combination. Cells were inoculated in female nude mice. Established tumors were treated with the micellar formulations at a dose of 4 mg/kg CUR and 0.4 mg/kg DOX every 2 d for a total of 7 injections.

Results: CUR + DOX-loaded micelles decorated with GLUT1 had a robust killing effect even at low doses of DOX in vitro. At the doses chosen, non-targeted CUR and CUR + DOX micelles did not exhibit any significant tumor inhibition versus control. However, GLUT1-CUR and GLUT1-CUR + DOX micelles showed a significant tumor inhibition effect with an improvement in survival.

Conclusion: We showed a dramatic improvement in efficacy between the non-targeted and GLUT1-targeted formulations both in vitro and in vivo. Hence, we confirmed that GLUT1-CUR + DOX micelles are effective and deserve further investigation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Curcumin / administration & dosage
  • Doxorubicin / administration & dosage
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Female
  • Glucose Transporter Type 1 / antagonists & inhibitors
  • HCT116 Cells
  • Humans
  • Mice
  • Mice, Nude
  • Micelles
  • Phosphatidylethanolamines / chemistry
  • Polyethylene Glycols / chemistry
  • Survival Rate
  • Xenograft Model Antitumor Assays

Substances

  • Drug Carriers
  • Glucose Transporter Type 1
  • Micelles
  • Phosphatidylethanolamines
  • SLC2A1 protein, human
  • dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine
  • Polyethylene Glycols
  • Doxorubicin
  • Curcumin